It has been reported that the known iridoids genipin represented by the following formula (II) and aucubin represented by the following formula (III) are natural substances, and act as a therapeutic agent for hepatitis B through the mechanism to inhibit the HBV replication (see, Korean Patent Laid-open No. 94-1886). ##STR3##
Said genipin of formula (II) and aucubin of formula (III) have some in vivo activities such as liver-protection, inhibition of biosynthesis of RNA and protein, detoxification as well as antiviral activity. Particularly, it has been disclosed that genipin is also effective as an anti-tumor agent (see, Japanese Patent Laid-open No 80/164625). However, these compounds may be decomposed to dialdehydes in vivo and the dialdehydes thus produced may combine with amino acid residues of proteins such as albumin. Such a series of reactions may induce some color change of urine, faces, and various internal organs into blue as well as immunotoxicities.
Compounds having a similar structure to the compound according to the present invention include the compound represented by the following formula (IV) in addition to genipin and aucubin(see, WO 92/06061 and European Patent Laid-open No. EP-0505572): ##STR4## in which R.sub.1 represents benzoyloxy, hydroxy, acetoxy or ethoxyethoxy, and
It is described in the above literatures that the compound of formula (IV) above may be used effectively as a therapeutic agent for hyperlipemia or as a cholagogues.
On the other hand, the present inventors have synthesized a series of novel aucubin and genipin derivatives on the basis of the prior arts as mentioned above in order to develop compounds having a superior activity to the earlier compounds on inhibition against HBV. After the antiviral activity and little cytotoxicity of the novel compounds prepared were identified, the present inventors have filed a patent application on the novel compounds (see, Korean Patent Appln. No. 95-38181).